OVERALL - Project Summary/Abstract Among viruses that cause disease in humans the filoviruses, Ebolavirus and Marburgvirus, stand out for their impressive lethality. These viruses are the most deadly human pathogens known to man with reported case fatality rates of up to 90%. The recent unprecedented 2013-16 epidemic of Zaire ebolavirus in West Africa resulting in over 28,000 cases and 11,000 deaths demonstrates the ability of filoviruses to emerge in new regions. In addition to natural outbreaks, Ebolavirus and Marburgvirus are known to have been the subjects of former biological weapons programs and have the potential for deliberate misuse. Currently, there are no filovirus vaccines or treatments approved for human use. For these reasons Ebolavirus and Marburgvirus have recently been included as only two of eleven human pathogens on the new US Department of Health and Human Services (HHS) Tier 1 list of Category A select agents. All three Research Projects (RP) that comprise the Center focus on developing broad spectrum rapid acting vaccines or therapeutics against all medically relevant variants and species of the family Filoviridae. RP1 employs recombinant vesicular stomatitis virus (VSV)-based rapid acting vaccines, RP2 focuses on fully human anti-filovirus monoclonal antibodies, and RP3 focuses on anti-filovirus small interfering RNAs, small molecule antivirals (GS-5734 and favipiravir), and combination treatments. A unique aspect of this Center is that these approaches represent a very small cohort of medical countermeasures that have shown the ability to provide complete single injection vaccination or therapeutic protection of nonhuman primates against filoviruses. This level of readiness is a major strength and consequential advantage of our Center. The primary objective of the Advancement of Vaccines and Treatments for Filovirus Infections Center is to perform ?well documented? and also ?pivotal? NHP studies that will facilitate the development of products used for the broad spectrum treatment of filovirus infections. The synergy and cooperation among the three RPs, the Administrative Core, and the Biosafety Level (BSL)-4 Core is built into the Center by design as all three RPs work together to assess and combine countermeasures for enhanced efficacy. Quality system data management will be employed in both the preparation of advanced stage test articles and in the conduct of animal studies.